卷 12, 编号 1 (2018)

Production of adrenal steroid hormones in pubertal male Wistar rats exposed to low doses of DDT during both prenatal and postnatal and only postnatal development has been investigated. Rats exposed to the disruptor prenatally and postnatally, and only postnatally were characterized by opposite changes in production of mineralocorticoids, glucocorticoids, male and female sex hormones. The study revealed that daily exposure to low doses of DDT enhanced conversion of progesterone to 17-OH-progesterone and did not exert selective antiandrogenic or proestrogenic action typical for the effect of toxic and subtoxic doses. In rats, exposed to DDT during their prenatal and postnatal development, impaired morphogenesis of the adrenal cortex and circulatory disorders in zona glomerulosa contributed to reduced aldosterone and sex steroid hormones production.

The search and research of pharmacological agents that could combine lipid-lowering and antithrombotic effects on the human organism are one of the most urgent and important tasks of modern biological and medical research. The unique effects of the regulatory peptides of the oxoproline series (5-охо-Pro- His-Pro-NH₂, 5-oxo-Pro-Trp-Pro, and 5-oxo-Pro-Arg-Pro or Pyr-His-Pro-NH₂, Pyr-Trp-Pro, and Pyr- Arg-Pro) synthesized by the methods of classical peptide chemistry have been found in animals with experimental hypercholesterolemia. Repeated intranasal administration of these peptides to animals with developed hypercholesterolemia increased their anticoagulant, fibrinolytic and antiplatelet potential of the blood and simultaneously lowered increased concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In addition, they promoted normalization of blood glucose. A week after the last administration of these peptides, the hypocholesterolemic, normoglycemic and anticoagulant effects persisted. The relationship between the structure of the oxoproline-containing peptides and their functional properties is discussed. It is concluded that further studies of oxoproline-containing peptides are promising in the context of development of pharmacological agents, combining the antithrombotic activity with the improvement of lipid metabolism in the body.

Chemerin is an adipose tissue mediator involved in the regulation of many processes, including lipogenesis, inflammatory responses, etc. The role of chemerin in the development of insulin resistance still needs better understanding. The aim of the study was to investigate chemerin production in obese patients with different states of carbohydrate metabolism. The study included 155 patients with diagnosed obesity and 34 patients with overweight. The control group 1 consisted of 43 conditionally healthy donors without obesity. For comparison of the research data on evaluation of tissue-specific mRNA expression of the genes IL-6, TNF-α, RARRES2, (encoding IL-6, TNF-α, and chemerin, respectively) control group 2 consisting of 30 non-obese was also included into this study. The relative level of mRNA expression of the genes IL-6, TNF-α and RARRES2 (encoding IL-6, TNF-α and chemerin, respectively) was carried out using real time PCR. Concentrations of IL-6, TNF-α, and chemerin were measured in serum/plasma using an enzymelinked immunosorbent assay (ELISA). Significant differences were found in the plasma level of chemerin and tissue-specific patterns of RARRES2 gene expression in obese patients; these changes depended on the degree of obesity and the state of carbohydrate metabolism. Opposite associations between RARRES2 gene expression and expression TNF-α and IL-6 genes have been recognized in adipose tissues of different localization: in obese patients (BMI ≤ 40 kg/m²) without type 2 diabetes mellitus (DM2) they were negative, while in obese patients with DM2 diabetes they were positive. The recognized correlations between the plasma content of chemerin and the expression level of its gene in biopsies with various parameters of carbohydrate and lipid metabolism, and proinflammatory molecules indicate chemerin involvement in metabolic and immune processes in obesity.

Properties and mechanisms of PCNA (proliferating cell nuclear antigen) functions have been investigated for a long time and are studied in great detail. As follows from its name, most known PCNA functions (DNA replication, DNA repair, DNA recombination and others) are connected with cell proliferation and localization of this protein in nuclei. In addition, there is good reason to believe that PCNA also performs some functions in the cytoplasm. However, the possible role and mechanisms of PCNA action in the cytoplasm require careful study and clarification. Interestingly, such cells as neutrophils differ in that they are non-dividing on one hand and on the other hand contain a rather large amount of PCNA, which is localized only in the cytoplasm, that is, they are an ideal model for the study of cytoplasmic PCNA. Using cross-linkages with formaldehyde, we showed that this cytoplasmic PCNA is cross-linked in a similar way, that is, organized in the same way as the nuclear PCNA that is present in the proliferating cells. Previously, we showed that PCNA in such cells is organized into a dynamic complex of double trimer on the basis of the back-toback principle. Apparently, such organization of this hub-protein allows it to better coordinate the processes taking place in the cytoplasm as well.

Comparative analysis of expression of genes encoding enzymes of catecholamine catabolism (monoamine oxidases A and B (MAO A and MAO B) and catechol-O-methyl transferase (COMT)) and renalase has been carried out in tissues of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Among investigated tissues the highest level of mRNA of genes encoding key enzymes of catecholamine catabolism (MAO A, MAO B, COMT) was found in the heart of WKY rats. In SHR the mRNA levels of these genes were lower (p < 0.05–0.01), however, no similar changes were observed in the tissues studied in dependence of hypertension. The relative mRNA levels of the studied genes normalized versus actin mRNA significantly varied. In heart and kidney the relative level of COMT mRNA significantly exceeded the relative levels of both MAO A mRNA and MAO B mRNA. In the brain differences in mRNAs of MAOA, MAOB, and COMT were less pronounced. However, in all examined tissue the renalase mRNA level was much (at least 10–20-fold) lower than any other mRNA studied. Taking into consideration known correlations between mRNAs and corresponding protein products reported in the literature for many genes these results suggest that in the case of any catalytic scenarios proposed or even proved for renalase this protein cannot contribute to catecholamine degradation. It is also unlikely that the products of the renalase reaction, β-NAD(P)⁺ and hydrogen peroxide, can exhibit a hypotensive effect due to low expression of the renalase encoding gene.

Gliomas are invasive brain tumors characterized by high rates of recurrence and mortality. Glioblastoma multiforme (GBM) is the most aggressive form of glioma with nearly 100% rate of recurrence and unfavorable prognosis in patients. MicroRNAs (miR) are a class of wide-spread short noncoding RNAs that inhibit translation via binding to the mRNA of target genes. The aim of this review is to analyze studies and experimental results on changes in the expression profiles of microRNA which are characteristic for gliomas/ glioblastomas and targeted to components of signaling pathways Hedgehog, Notch, Wnt, EGFR, TGFβ, and HIF1α, aberrantly regulated in the gliomas. Special attention has been paid to the links of microRNA to the targets of 2-hydroxyglutarate, the product of mutant isocitrate dehydrogenase (R132H IDH1), mutational changes of which are specific for the pathogenesis of gliomas. Detection of certain types of microRNA in tissues and blood serum can be used for diagnostics and prediction, including responsiveness of individual patients to therapy, and development of new therapeutic strategies.